Title:Target Driven Preclinical Screening for New Antimitotic Chemotherapy Agents
Volume: 14
Issue: 20
Author(s): S. Novio, M. Freire-Garabal and M.J. Núnez
Affiliation:
Keywords:
Cancer, drug development, kinase, kinesin, mitosis, multiprotein complexes.
Abstract: Currently approved antimitotic therapies used in chemotherapy are microtubule-targeting agents
(MTAs). Despite they achieved some level of success, they have limited efficacy as single agents, with issues
of slippages and resistance, and cause significant side effects. The advances in the identification of
other mitosis-related targets led to the development of new mitotic regulators aimed to perturb mitosis without
interfering with microtubule dynamics in non-dividing cells trying to reduce side effects in patients. Some of these
compounds like those targeted to entry and mitotic kinases, mitotic kinesins/motor proteins, and multiprotein complexes
have been evaluated in vitro and in animal models, and some of them have reached clinical trials. Despite promising preclinical
results, in many cases, the efficacy demonstrated by these new antimitotics was not better than current microtubule
inhibitors. In this paper we review present and future strategies on the search for new antimitotic compounds based
on identification of new protein targets and development of multifunctional inhibitors of mitosis in cancer cells.
